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Title: Human anti-murine antibody responses in ovarian cancer patients undergoing radioimmunotherapy with the murine monoclonal antibody OC-125

Human anti-murine antibody (HAMA) responses were monitored in 23 patients with recurrent or persistent epithelial ovarian carcinoma undergoing single-dose intraperitoneal radioimmunotherapy (RIT) with the murine monoclonal antibody OC-125. Sera of patients receiving escalating doses of OC-125 F(ab')2 (10-70 mg) radiolabeled with 18 to 141 mCi of iodine-131 were assayed for HAMA by a protein A-based radioimmunoassay. Overall, 70% of patients (16/23) developed HAMA within 10 to 46 days (median = 29) postinfusion, with peak values (23 +/- 6 to 325 +/- 10 micrograms/ml) at 32 to 102 days (median = 38). HAMA was undetectable prior to infusion in all cases and persisted up to 76 weeks. Of patients receiving a dose of 123 mCi or less, 80% (16/20) developed HAMA, whereas in the 140-mCi group, none of the three patients had detectable levels. Two patients in the 140-mCi group demonstrated dose-limiting bone marrow toxicity (severe thrombocytopenia and neutropenia). It is concluded that a single intraperitoneal dose of monoclonal antibody leads to a high incidence of HAMA production. The results also suggest that the likelihood of HAMA formation in patients who either had undergone recent chemotherapy or had received the highest dose of the radioimmunoconjugate is reduced. These observations may bemore » of significance in designing multiple-dose therapy trials as HAMA has been demonstrated to decrease antibody-to-tumor binding and may potentially increase renal, hepatic, and hematologic toxicity associated with radioimmunotherapy.« less
Authors:
; ; ; ;  [1]
  1. (Brigham and Women's Hospital, Boston, MA (USA))
Publication Date:
OSTI Identifier:
6758754
Resource Type:
Journal Article
Resource Relation:
Journal Name: Gynecologic Oncology; (USA); Journal Volume: 38:2
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; RADIOIMMUNOTHERAPY; OVARIES; EPITHELIUM; INTRAPERITONEAL INJECTION; IODINE 131; MAN; MONOCLONAL ANTIBODIES; PATIENTS; RADIOIMMUNOASSAY; ANIMAL TISSUES; ANIMALS; ANTIBODIES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOASSAY; BODY; DAYS LIVING RADIOISOTOPES; DIAGNOSTIC TECHNIQUES; DISEASES; FEMALE GENITALS; GONADS; IMMUNOASSAY; IMMUNOLOGY; IMMUNOTHERAPY; INJECTION; INTAKE; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; MAMMALS; MEDICINE; NEOPLASMS; NUCLEAR MEDICINE; NUCLEI; ODD-EVEN NUCLEI; ORGANS; PRIMATES; RADIOASSAY; RADIOIMMUNODETECTION; RADIOIMMUNOLOGY; RADIOISOTOPES; RADIOLOGY; RADIOTHERAPY; THERAPY; TISSUES; TRACER TECHNIQUES; VERTEBRATES 550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)